food industry wastes || functional food and nutraceuticals derived from food industry wastes

C H A P T E R

6

Functional Food and Nutraceuticals Derivedfrom Food Industry Wastes

Maria R. Kosseva

1. INTRODUCTION

Vegetables and fruits are known to contain compo-nents, such as vitamins, essential minerals, antioxi-dants, and prebiotics (fibers), with several types ofhealth-promoting actions, and most of these have beenevaluated in intervention studies. Many epidemio-logical studies show negative correlations between theintake of vegetables and fruits and the incidence ofseveral important diseases, including cancer andatherosclerosis (Kris-Etherton et al., 2002; Gundgaardet al., 2003; Maynard et al., 2003; Trichopoulou et al,2003). Optimization of composition of plant-derivedfood would be a very cost-effective method for diseaseprevention, since diet-induced health improve-ments would not carry any added costs for the healthsector (Gundgaard et al., 2003). If improvements canbe obtained with existing or slightly adapted foodtechnology, the production costs will be similar(Brandt et al., 2004).

The current global market size of functional foods hasalready reached $73.5 billion from a modest base just10 years ago (www.just-food.com, 2006). The US marketdominates (.30% of the total global market) and isshowing a sustained growth of B14% per year. Othersignificant markets include the EU and Japan. Growth inthe functional foods market across the world is currentlyB8% per year, and at this rate the market will be valuedat .$100 billion by 2012. In this large and burgeoningmarketplace, the food industry is demanding economi-cal, high-quality, novel, and substantiated ingredients(Smithers, 2008).

The first part of this chapter is focused on functionalfoods/nutraceuticals derived from fruit-and-vegetablewaste (FVW) and phytochemical extraction methods.Then a brief overview of bioactive peptides and their

occurrence in whey and dairy by-products is provided.Finally, consumer acceptance of the concept of functionalfoods is recognized as a key success factor for new prod-uct development and market orientation.

1.1 Definition of Nutraceuticals and FunctionalFood

Products isolated or purified from food but that aregenerally sold in medicinal forms not usually associ-ated with food, such as capsules, are referred to asnutraceuticals. Nutraceuticals are demonstrated to havea physiological benefit or provide protection againstchronic disease. A working definition of nutraceuticalfrom a Science forum states: “a diet supplement thatdelivers a concentrated form of a biologically activecomponent of food in a non-food matrix to enhancehealth” (Zeisel, 1999). This distinguishes nutraceuticalsfrom functional foods, which according to the forum:“are consumed as part of a normal diet and deliver oneor more active ingredients (that have physiologic effectsand may enhance health) within the food matrix”.

The European Commission’s Concerted Action onFunctional Food Science in Europe (FuFoSE), coordi-nated by the International Life Science Institute (ILSI)Europe, defined functional food as follows: “a foodproduct can only be considered functional, if togetherwith the basic nutritional impact it has beneficialeffects on one or more functions of the human organ-ism thus either improving the general and physicalconditions or/and decreasing the risk of the evolutionof diseases. The amount of intake and form of thefunctional food should be as it is normally expectedfor dietary purposes. Therefore, it could not be in theform of pill or capsule just as normal food form”(Diplock et al., 1999). Contrary to this latter statement,

103Food Industry Wastes.

DOI: http://dx.doi.org/10.1016/B978-0-12-391921-2.00006-8 © 2013 Elsevier Inc. All rights reserved.

http://dx.doi.org/10.1016/B978-0-12-391921-2.00006-8

since 2001 FOSHU (Food for Specified Health Uses)products in Japan can also take the form of capsulesand tablets like nutraceuticals, although a great major-ity of products are still in more conventional forms(Ohama et al., 2006).

European legislation, however, does not considerfunctional foods as specific food categories but ratheras a concept (Coppens et al., 2006). According to theEuropean regulation on nutrition and health claimsmade on foods (EC No.1924/2006), a list of authorizedclaims has to be published for all member states, andnutrient profiles also have to be established for foodscontaining health claims (Siro et al., 2008). Bagchi(2006) has discussed relevant legislation in the USA.

2. PHENOLIC COMPOUNDS DERIVEDFROM FRUIT-AND-

VEGETABLE PROCESSING WASTES

The beneficial effects of plant-derived food areattributed mainly to high-molecular-weight dietaryfiber on one hand, and low-molecular-weight second-ary plant metabolites on the other. The latter compo-nents are chemically very heterogeneous and comprisecarotenoids, polyphenols, glucosinolates, saponins,alkaloids, and so on. The polyphenols are broadly clas-sified into phenolic acids (hydroxybenzoic and hydro-xycinnamic acids), flavonoids, xanthones, andstilbenes and constitute an extremely diverse class ofsecondary metabolites. They have been associated witha number of health-promoting properties such as anti-oxidant, anticarcinogenic, anti-inflammatory, antidia-betic, antithrombotic, and vasoprotective activities.

Why are wastes from fruit-and-vegetable (FV) pro-cessing such a rich source of bioactive compounds?The trend to produce functional foods by adding bio-active compounds has entailed numerous investiga-tions on the extraction of secondary plant metabolites,which in turn raises the question as to the sources ofthese components. In this context, wastes from FV pro-cessing such as peels, seeds, and stems have attractedintense interest during the past decade. Depending onthe raw material and the technologies applied, theyemerge in large quantities and are often a considerabledisposal problem for the food industry. For example,during wine and apple juice production, approxi-mately 20% and 35% respectively of the raw materialremains as pomace. Even higher proportions of by-products emerge from processing of some exotic fruitssuch as mangoes, where the peels and seeds mayamount to up to 60% of the total fruit weight.Secondary plant metabolites such as polyphenols playan important role in the defense system of the plant,protecting it from biotic and abiotic stress. For

example, flavonoids act as UV absorbing compoundsand signal molecules. Phenolic compounds also showantimicrobial activity against plant pathogens. Becauseof their biological role in plants, secondary metabolitesare located primarily in the outer layers of fruits andvegetables and in the seeds. During processing, theseplant parts are usually removed by peeling or areretained in the press residues (e.g. skins and seeds ingrape pomace). For this reason, the by-products con-tain large amounts of secondary plant metabolites inconcentrated form and represent promising sources ofbioactive compounds, which may be included in func-tional foods. Because of their high water contents, theby-products are prone to microbial spoilage and needto be dried immediately after processing, which is aneconomically limiting factor (Schieber, 2009).

Selected sources of FV processing residues and themajor fractions of phenolics are shown in Table 6.1.

2.1 Flavonoids

The flavonoids are a group of plant metabolites thatare the most common group of polyphenolics in thehuman diet (Figure 6.1). They are subdivided into several

TABLE 6.1 Waste from Fruit-and-Vegetable Processing as aSource Of Phenolic Compounds

FV-derived

By-products Phenolic Compounds (Major Fractions)

FRUIT-DERIVED

Apple pomace Chlorogenic acid, quercetin glycosides,dihydrochalcones, flavanols

Black currantresidues

Anthocyanins

Blueberryprocessing waste

Anthocyanins, hydroxycinnamates, flavonolglycosides

Cranberry pomace Caffeic acid, ellagic acid

Grape pomace Anthocyanins, flavonol glycosides, stilbenes,phenolic acids

Mango peels/kernels

Flavonol glycosides, xanthone glycosides,hydrolyzable tannins, alk(en)ylresorcinols

Star fruit residues Procyanidins

VEGETABLE-DERIVED

Artichoke pomace Hydroxycinnamates, flavonoids

Cauliflower by-products

Kaempferol glycosides, hydroxycinnamates

Olive mill waste Oleuropein, hydroxytyrosol, verbascoside,dihydroxyphenylglycol

Onion peels Quercetin glycosides

Potato peels Phenolic acids

Adapted from Schieber (2009).

104 6. FUNCTIONAL FOOD AND NUTRACEUTICALS DERIVED FROM FOOD INDUSTRY WASTES

II. TREATMENT OF SOLID FOOD WASTES

other groups including flavone, flavonol, flavanone, andisoflavones. Isoflavonoids differ from other flavonoids byhaving ring B attached to the C-3 position of ring C (e.g.,puerarin, daidzein, and genistein). In plants, they areespecially important in guarding against oxidant dam-age, and they provide to the plant the color that attractspollinators and repels attacks by insects and microbes.

Recent research suggests that, in humans, these plantpolyphenols provide important health benefits related tometabolic syndrome, cancer, brain health, and theimmune system. The relatively low toxicity and potentialefficacy of most of these agents make them attractive to alarge sector of the population. While dietary flavonoidsare primarily obtained from soy, many are found infruits, nuts, and more exotic sources. Perhaps the stron-gest evidence for the benefits of flavonoids in diseases ofaging relates to their effect on components of the meta-bolic syndrome. Flavonoids from grape seed, soy, kudzu(Pueraria lobata) roots, and other sources all lower arterialpressure in hypertensive animal models and in a limitednumber of tests in humans. They also decrease theplasma concentration of lipids and buffer plasmaglucose. The underlying mechanisms appear to include

antioxidant actions, central nervous system effects,gut transport alterations, fatty acid sequestration andprocessing, peroxisome proliferators-activated receptor(PPAR) activation, and increases in insulin sensitivity.In animal models of disease, dietary flavonoids alsodemonstrate a protective effect against cognitive decline,cancer, and metabolic disease. However, research alsoindicates that the flavonoids can be detrimental in somesettings and, therefore, are not universally safe. Thus, asthe population ages, it is important to determine theimpact of these agents on prevention of disease, includ-ing optimal exposure (intake, timing/duration) andpotential contraindications (Prasain et al., 2010).

The citrus flavonoids, naringin, and naringenin, werefound to significantly lower the expression levels ofvascular cell adhesion molecule-1 (VCAM-1) and mono-cyte chemotactic protein-1 (MCP-1), with potentialapplications in the prevention of atherosclerosis (Leeet al., 2001). Bioflavonoids like hesperidin (from orangepeel), naringin (grapefruit peel), or rutin can normalizecapillary permeability and vascular brittleness, thereforethey are frequently called vitamin P factors. Hesperidinis applied in vein medication, acts as an antiviral in flu

Puerarin Daidzin Genistin

OHO

OOGlucose

O

OHO

OGlucose

OH

Apigenin

OOH

HO

OH O

Glycitein

OHO

O

H3CO

OH

Coumestrol

OHO

OOH

O

O

OHO

HO

Glucose

(+) catechin

Proanthocyanidin B2

Quercetin

OHO

OH

OH

O

OH

OH

OHO

OH

OH

OH

OH

OHO

HO

OH

OH

OH

O

OH

OH

OH

OH

OH

FIGURE 6.1 Chemical structures of some dietary flavonoids. Source: Prasain et al. (2010).

1052. PHENOLIC COMPOUNDS DERIVED FROM FRUIT-AND-VEGETABLE PROCESSING WASTES


therapy, and possesses artificial sweetener properties;hydrated naringin is about 300 times sweeter than sac-charose, neohesperidin almost 2000 times (Laufenberget al., 2003).

2.2 Polyphenol Content of Grape Wine Wastes

The phenolic compounds of wine, particularly theflavanols (e.g., catechins, proanthocyanidins), havebeen the focus of a number of studies because of theirrelation to the beneficial effects attributed to a moder-ate consumption of wine (Shrikhande, 2000). Thesecompounds have their origin in grape, and only a partof them is transferred to the must. Their extractabilitymainly depends on the technological conditions duringvinification (Kammerer et al., 2004). For this reason,important quantities of phenolic compounds stillremain in the wine by-products and there is greatinterest in the exploitation of this type of grape by-product to obtain potentially bioactive phenolic com-pounds (Santos-Buelga and Scalbert, 2000; Moureet al., 2001; Ray et al., 2001). Grape seeds are an abun-dant source of proanthocyanidins with varyingdegrees of polymerization, which find application asnutraceuticals in numerous products. In the USA,grape seed extracts have GRAS status, which meansthat they are generally recognized as safe. Pomacefrom red wine production has long been used for theextraction of anthocyanins, which are the red and bluepigments also found in cranberry, elderberry, blue-berry, blackberry, black currant, strawberry, red cab-bage, and purple carrots. The highest concentrations ofgrape polyphenols are found in the skin, stems, andseeds (Table 6.2).

2. 2. 1 Proanthocyanidins

Proanthocyanidins are a class of compounds thatare found in many plants and that can be extractedfrom grape seed. Their basic structural unit is catechin(Figure 6.1). Proanthocyanidins contain catechin

monomer, dimer, and trimer, all of which are water-soluble molecules that contain a number of phenolichydroxyls (Bagchi et al., 2002). Polyphenolic com-pounds have a very important antioxidant function;they can clean off free radicals in the body and reducemembrane lipid peroxidation, so they can reduce theoccurrence of free-radical-related diseases and possiblydelay aging (Morillas-Ruiz et al., 2006; Iacopini et al.,2008). Current studies have shown that grape seedproanthocyanidin extract can neutralize free radicals,protect the over-oxidative damage caused by free radi-cals (Feng et al., 2005; Spranger et al., 2008), andreduce the incidence of a range of diseases caused byfree radicals, such as myocardial infarction, atheroscle-rosis, and drug-induced liver and kidney injury.Moreover, they have antithrombotic, antitumor, anti-mutagenic, anti-radiation-damage, and antifatigueeffects (Yamakoshi et al., 1999; Sano et al., 2005;Engelbrecht et al., 2007).

Shan et al. (2010) carried out a preliminary study ofthe effect of grape seed proanthocyanidin extract(GSPE) on the free radical and energy metabolismindicators during movement. The extract rate ofproanthocyanidins was 6.17%, according to Feng andChen (2003). They explored the antifatigue mechanismof GSPE with regard to antioxidation system andenergy metabolism, trying to provide theoretical guid-ance and experimental evidence for using GSPE insport practice. Their results show that GSPE can signif-icantly increase the activity of antioxidant enzymes inmice and clear free radicals in the body, so it can pro-tect the body against free-radical damage. At the sametime, GSPE can affect glucose metabolism in mice,increase the liver and muscle glycogen reserves,reduce the consumption of glucose, and keep the levelof blood glucose stable. In addition, GSPE can affectfat metabolism in mice and promote the utilization offat.

2. 2. 2 Resveratrol

Resveratrol is found abundantly in the skin ofgrapes; peanuts, itadori tea, and wine also contain res-veratrol in appreciable amounts (Burns et al., 2002).Among the non-flavonoid polyphenolic compounds,trans-resveratrol (3, 40, 5-trihydroxy-trans-stilbene), usedfor analgesic and therapeutic purposes in oriental folkmedicine (Pace-Asciak et al., 1995), has been proposedas one of the components in red wine that mightconfer specific protection against coronary heartdisease (CHD). Preliminary evidence from experi-mental animals (Kimura et al., 1983) and more recentin vitro studies on human plasma (Frankel et al., 1993)suggest that its antioxidant activity might also be rele-vant in vivo. Moreover, in vitro antiplatelet activity of

TABLE 6.2 Quantity of Total Phenolic Substances, TotalFlavanoids, and Proanthocyanidins Reported in Grape Extractand Grape Seeds

CompoundsQuantity in GrapeExtract (g/L)

Quantity in

Grape Seeds(g/100 g DM)

Total phenols (GAE) 2.866 0.01 8.586 0.03

Total flavanoids (CE) 2.796 0.01 8.366 0.04

Proanthocyanidins (CyE) 1.386 0.06 5.956 0.17

Source: Adapted from Negro et al. (2003)CE, catechin equivalent; GAE, gallic acid equivalent; CyE, cyanidin equivalent.



trans-resveratrol has been observed and subsequentlyconfirmed (Rotondo et al., 1998).

The additional parts of the grape such as the skin,the whole grape by itself, grape-derived raisins, andphytochemicals present within the grapes have alsodemonstrated potential anticancer efficacy in variouspreclinical and clinical studies. The underlyingmechanisms of action of these grape-waste productsare summarized by Kaur et al. (2009).

Experimental studies (Dohadwala and Vita, 2009)indicate that grape polyphenols could reduce athero-sclerosis by a number of mechanisms, including inhibi-tion of oxidation of low density lipoprotein (LDL) andother favorable effects on cellular redox state, improve-ment of endothelial function, lowering of bloodpressure, inhibition of platelet aggregation, reducinginflammation, and activating novel proteins that pre-vent cell senescence (e.g., Sirtuin 1). Translationalstudies in humans support these beneficial effects.More clinical studies are needed to confirm these effectsand formulate dietary guidelines. The available data,however, strongly support the recommendation that adiet rich in fruits and vegetables, including grapes, candecrease the risk of cardiovascular disease. In vitrostudies have shown that grape-derived polyphenolsinhibit platelet activity, and a number of potentialmechanisms have been elucidated. Flavonoids inhibitcyclooxygenase and reduce production of thromboxaneA2. Red wine polyphenols also decrease platelet pro-duction of hydrogen peroxide and inhibit activation ofphospholipase C and protein kinase C (Pignatelli et al.,2000).

2. 2. 3 Anthocyanins

Anthocyanins are a group of phenolic compoundsthat belong to the flavanoid family. They are responsi-ble for the coloration (orange, rose, red, violet, andblue) of the petals of flowers and fruit of a greatvariety of plants (Strack and Wray, 1989). There arenumerous sources of anthocyanins, but the main rawmaterial is the pomace from the red wine vinificationprocess (Table 6.3). Currently, the European Unionallows the use of anthocyanins as food dyes in drinks,marmalades, candies, ice creams, and pharmaceuticalproducts (EU, 1994).

2.3 Polyphenols in Apple Pomace

Apple pomace contains various types of polyphenols,especially chlorogenic acid, dihydrochalcone derivatives,quercetin glycosides, and flavanols. A number of studiesindicate that phenolic compounds from apples mightreduce the risk of colon cancer because of their antioxi-dative and antiproliferative activities and by favourablymodulating gene expression. Therefore, the extraction ofpolyphenols for use as functional food ingredientsappears to be a promising approach (Schieber et al.,2001).

3. VEGETABLE FLAVONOIDS

3.1 Onion Flavonoids

Awide variety of flavonoids are distributed in vegeta-bles. Onion bulbs (Allium cepa L.) are among the richestsources of dietary flavonoids and contribute to a largeextent to the overall intake of flavonoids. Flavonoidscontinue to attract attention as potentially useful agentswith implications for inflammation, cardiovascular dis-eases, and cancer (Middleton et al., 2000; Okamoto,2005). In their review, Slimestad et al. (2007) report acompilation of more than 50 flavonoids identified in pig-mented scales of onions. The majority of these structureshave been confirmed through NMR investigations.

3.2 Flavonols of Onions

Flavonols are the predominant pigments of onions.From ancient times, dried pigmented scales of onionshave been used to provide yellow coloration to textilesand Easter eggs. Flavonols are the main flavonoids ofpigmented scales of onions. The main flavonols arebased on quercetin (3, 5, 7, 30, 40-pentahydroxyflavone)(Box 6.1). The structural diversity of the minor flavo-nols of onions is extensive and includes derivatives ofkaempferol, isorhamnetin, and possibly myricetin.Altogether at least 25 different flavonols have been

TABLE 6.3 Anthocyanin Content of Grape Skins

Compound Value (mg/kg DM)

Delphinidin 3-O-glucoside 68�5552

Cyanidin 3-O-glucoside 37�1903

Petunidin 3-O-glucoside 65�6680

Peonidin 3-O-glucoside 515�12,450

Malvidin 3-O-glucoside 1117�50,981

Delphinidin 3-O-acetglucoside 392�956

Petuidin 3-O-acetglucoside 545�1375

Peonidin 3-O-acetglucoside 1371�1484

Peonidin 3-O-acetglucoside 45�8688

Cyanidin 3-O-coumaroylglucoside 374�1071

Petunidin 3-O-coumaroylglucoside 974�2458

Peonidin 3-O-coumaroylglucoside 68�6828

Source: Adapted from Kammerer et al. (2004).



characterized from onion bulbs. The glycosyl unit(s) ofthese pigments has in most cases been identified asglucose. Most of the anthocyanins reported to occur invarious cultivars of red onion are cyanidin derivatives.The main anthocyanins of all cultivars investigatedare exclusively glycosylated at the anthocyanidin3-position. Yellow onions contain 270�1187 mg of fla-vonols per kilogram of fresh weight, whereas redonions contain 415�1917 mg of flavonols per kilogramof fresh weight. The anthocyanins of red onions aremainly cyanidin glucosides acylated with malonic acidor non-acylated. Some of these pigments facilitateunique structural features like 40-glycosylation andunusual substitution patterns of sugar moieties.Altogether at least 25 different anthocyanins havebeen reported from red onions, including two novel5-carboxypyranocyanidin-derivatives. The quantitativecontent of anthocyanins in some red onion cultivarshas been reported to be approximately 10% of the totalflavonoid content or 39�240 mg/kg fresh weight.

At least 25 different flavonols have been character-ized, and quercetin derivatives are the most importantones in all onion cultivars. Their glycosyl moieties arealmost exclusively glucose, which is mainly attached tothe 40, 3, and/or 7-positions of the aglycones. Quercetin40-glucoside and quercetin 3, 40-diglucoside are in mostcases reported as the main flavonols in recent literature.Analogous derivatives of kaempferol and isorhamnetinhave been identified as minor pigments. Recent reports

indicate that the outer dry layers of onion bulbs containoligomeric structures of quercetin in addition to con-densation products of quercetin and protocatechuicacid (Slimestad et al., 2007).

3.3 Functionality of Flavonoids

3. 3. 1 Prevention of Atherosclerosis andCardiovascular Disease

Quercetin 40-glusoside and quercetin 3, 40-digluco-side are exclusively present in onion, whereasquercetin 3-glucoside (isoquercitrin) and quercetin-3-rutinoside (rutin) are predominant glycosides incommon vegetables (Terao et al., 2008). Hertog et al.(1993) found that flavonoid intake was inversely corre-lated with CHD mortality in elderly men. Nowadays,epidemiological studies strongly suggest that theintake of flavonoids from diet is helpful in the preven-tion of atherosclerosis and its related events, includingCHD. However, the molecular mechanism for theiranti-atherosclerotic action and the absorption mecha-nism related to their bioavailability should be clarifiedfor the practical use of dietary flavonoids in loweringthe risk of atherosclerosis.

An ultimate target for dietary quercetin as anti-athero-sclerotic agent is undoubtedly the blood aorta, whereplaque formation happens in relation to atheroscleroticinjury. However, work on the accumulation of dietary

BOX 6.1

STRUCTURE OF QUERCET IN

OHo-dihydroxyl structure

(catechol group)

2, 3-double bond withconjugation to 4-oxo group

hydroxyl group at the 3and 5 position

OH

2

3′

4′B

O

435

OH

OH

O

HO

A C

Bors et al. (1990) were the first to claim three partial structures contributing to the radical-scavenging activity of

flavonoids: (a) o-dihydroxyl structure in the B ring (catechol structure) as a radical target site; (b) 2, 3-double bond

with conjugation to 4-oxo group, which is necessary for delocalization of an unpaired electron from the B ring, and

(c) hydroxyl groups at the 3 and 5 position, which are necessary for enhancement of radical-scavenging activity. The

circles indicate partial structures contributing to the free-radical-scavenging activity of flavonoids (Terao, 2009).



flavonoids in this target site is limited. Terao et al. (2008)designed an experiment using high cholesterol-fedrabbits to examine whether or not dietary quercetinactually accumulates in the aorta tissue and exerts anti-oxidant activity. By HPLC and HPLC-MS analyses, theydetected quercetin metabolites in the aorta tissue ofquercetin glucoside-fed rabbits. It is therefore likely thata high-cholesterol diet induces oxidative stress in theblood vessel and that quercetin metabolites contribute toan antioxidant network to counteract reactive oxygenspecies (ROS)-induced injury directly or indirectly.Recently the same researchers prepared a novel mono-clonal antibody, which specifically recognizes quercetinglucuronide, and succeeded in detecting quercetinglucuronides in human atherosclerotic aorta by animmunohisto chemical approach. Their findings suggestthat quercetin metabolites are incorporated into the athero-sclerotic region and act as complementary antioxidantswhen oxidative stress is loaded on the vascular system.It is likely that plasma albumin is a carrier for translocationof quercetin metabolites to the vascular target.

3. 3. 2 Antioxidant Activity

Although flavonoids in the diet have a bitter orastringent taste and inhibit digestive enzymes, recentstudies strongly suggest that dietary flavonoids mayhave a favorable role in human health through theirantioxidant activity (Hooper et al., 2008). Oxidativestress is frequently referred to as an essential factorin the initiation and/or promotion of degenerativediseases such as atherosclerosis. Much attention hastherefore been paid to the antioxidant activity of die-tary flavonoids from the viewpoint of food factors thatmodulate oxidative stress (Rice-Evans et al., 1996).Dietary flavonoids seem to participate in the antioxi-dant network together with vitamin E, vitamin C, andother biological antioxidants in the human body(Terao, 2009). Recent studies also suggest that dietaryflavonoids can exert various effects by a mechanismdifferent from classical antioxidant activity: regulationof the activity and protein expression of specificenzymes (Virgili and Marino, 2008).

The mechanism of antioxidant activity of flavonoidscan be characterized by direct scavenging or quench-ing of oxygen free radicals or excited oxygen speciesas well as inhibition of oxidative enzymes that gener-ate these reactive oxygen species. The essential part ofthe free radical-scavenging activity of flavonoids isattributed to the o-dihydroxyl group in the B ring (cat-echol group) in their diphenyl propane structure.Catechol type flavonoids therefore possess powerfulantioxidant activity (Terao, 2009).

Accumulation of flavonoid metabolites in the appro-priate target site is probably required to exert their anti-oxidant activity. Conversion of inactive metabolites to

active aglycones via a deconjugation reaction in the targetsite may be a key process for efficient exertion of theirantioxidant activity. The significance of dietary flavo-noids as antioxidants in vivo is much more complicatedthan that expected from in vitro assays. The specific targetshould be taken into account when evaluating the anti-oxidant activity of dietary flavonoids in vivo.

The levels of antioxidative quercetin derivatives areconsiderably higher in onion peels than in the flesh.Since onion flavonoids are readily absorbed, theycould contribute significantly to antioxidant defense.Protocols for their recovery based on subcritical waterextraction and water/ethanol/citric acid extractionhave recently been developed (Schieber, 2009).

3. 3. 3 Metabolic Syndrome

The strongest evidence for the benefits of flavonoids indiseases of aging relates to their effect on components ofthe metabolic syndrome. The metabolic syndrome hasthree major contributors: hypertension, dyslipidemia/obesity, and hyperglycemia/hyperinsulinemia, all ofwhich act synergistically to greatly increase morbidityand mortality (Prasain et al., 2010). While the incidence ofall three contributors is increasing exponentially inadults, a parallel rise is also occurring in children(Nathan and Moran, 2008). It is estimated that clusteringof these metabolic risk factors occurs in up to 50% ofoverweight adolescents, leading to an increased appear-ance in early onset type-2 diabetes and cardiovasculardisease (Nelson and Bremer, 2009). The treatment of met-abolic syndrome in both young and aging populationshas greatly increased pharmaceutical expenditures, andantihyperglycemic drugs are projected to become thelargest single component of all prescription drug spend-ing in the near future (Hoerger and Ahmann, 2008),making the metabolic syndrome a very significant bur-den on individual health and the economy. Research isincreasingly exploring the ability of botanical supple-ments to reduce metabolic syndrome risk factors, sincethese compounds could provide greater efficacy andtolerability at lower cost than current pharmaceuticaloptions (Figure 6.2).

3. 3. 4 Hormonal Activity

Currently, a broad range of phyto-pharmaceuticalswith a claimed hormonal activity, called phytoestrogens,is recommended for prevention of various diseasesrelated to a disturbed hormonal balance (Dijsselbloemet al., 2004). In this respect, soy isoflavones (genistein,daidzein, biochanin), as potential superior alternativesto the synthetic selective estrogen receptor modulators(SERMs), are currently applied in hormone replace-ment therapy (HRT). As phytochemicals integrate hor-monal ligand activities and interference with signalingcascades, therapeutic use may not be restricted to



hormonal ailments only, but may have applicationsin cancer chemoprevention and/or NF-κB-relatedinflammatory disorders as well.

Accordingly, intense investigations point to theimportant role of consumption of dietary soy, as themajor source of isoflavones, in low cancer incidence(Birt et al., 2001; Adlercreutz, 2002). ParticularJapanese population groups are estimated to registerthe highest intake of soy products, with levels up to200 mg/day. Generally, the Asian consumption oflegumes is assumed to supply 20�50 mg of isoflavonesin the daily diet, which sharply contrasts with thewestern negligible amount of less than 1 mg isofla-vones/day (Nagata et al., 1998). Consistent with theepidemiological studies are the findings that soy phy-toestrogens improve bone mass in peri- and postmeno-pausal women (Potter et al., 1998; Alekel et al., 2000).Furthermore, they prevent atherosclerosis of coronaryarteries in monkeys (Anthony et al., 1996) and signifi-cantly reduce cholesterol levels in hypercholesterol-emic subjects (Crouse et al., 1999).

4. COLORING AGENTS ANDANTIOXIDANTS

Anthocyanins, carotenoids, betalains, lycopenes,and leucoanthocyanidin represent the major groups ofcolored phenolic compounds in FV residues. They arepowerful antioxidants and may possess pharmacologi-cal properties, which could make them desirableingredients in the developing market of “functionalfoods” for health. For example, grape skin extract inpowder form is commercially available as a naturalfood-coloring agent. Besides the blue-red color, thefood will be enriched with “healthy” polyphenols(Laufenberg et al., 2003).

4.1 Betalains

More than 200,000 tonnes of red beet are producedin Western Europe annually, most of which (90%) isconsumed as vegetable (Schieber et al., 2001). Theremainder is processed into juice, coloring foodstuff,and food colorant, the latter commonly known asbeetroot red. Though still rich in betalains, the pom-ace from the juice industry, accounting for 15�30% ofthe raw material, is disposed of as feed or manure.The colored portion of the beetroot ranges from 0.4%to 2.0% of the dry matter, depending on intraspecificspecies, edaphic factors, and postharvest treatments.Whereas the colored fraction consists of betacyaninsand betaxanthins, the phenolic portion of the peelshows L-tryptophane, p-coumaric, and ferulic acids,as well as cyclodopa glucoside derivatives. Beets areranked among the 10 most potent vegetables withrespect to antioxidant capacity, ascribed to a totalphenolic content of 50�60 mmol/g dry weight.Toxicological studies reveal that betanin, the majorcompound from red beet, does not exert allergicpotential, nor mutagenic or hepatocarcinogeniceffects. High content of folic acid, up to 15.8 mg/gdry matter, is another nutritional feature of beets(Schieber et al., 2001).

4.2 Lycopenes

Skin, rich in lycopene, is an important component ofwaste originating from tomato paste manufacturingplants. Lycopene is the principal carotenoid, causingthe characteristic red hue of tomatoes. Several epide-miological studies have reported that lycopene-richdiets have beneficial effects on human health. A possi-ble role has been suggested for tomatoes and tomatoproducts in preventing cardiovascular disease andprotecting against some types of cancer (based onlycopene content). Maximum lycopene (1.98 mg/100 g)was extracted when the solvent/meal ratio adjusted to30:1 v/w, number of extractions 4, temperature 50�C,particle size 0.15 mm, and extraction time 8 min(Schieber et al., 2001).

5. DIETARY FIBERS

Numerous studies indicate that dietary fibers (DF)counteract obesity, cardiovascular disease, and type 2diabetes. DF also play an important role in the preven-tion and treatment of gastrointestinal disorders andlarge-intestine cancer (Champ et al., 2003). DF com-prise a combination of many compounds (pectin, lig-nin, cellulose) differing in physical and chemicalproperties. FV by-products such as apple, pear, orange,

Pancreatic β-cell damageInsulin insufficiency

Plaque formationEndothelial damage

Hypertension Diabetes Hyperlipidemia

Antioxidant, autonomic,vasodilator Antioxidant, PPAR,

glucose/insulinregulation Antioxidant, gut

alterations, PPAR

FIGURE 6.2 Mechanisms by which flavonoids are most likely toreduce the three main contributors to metabolic syndrome in aging

adults. Peroxisome Proliferator-Activated Receptor (PPAR). Source:Prasain et al. (2010).



peach, black currant, cherry, artichoke, asparagus,onion, and carrot pomace are used as sources of DFsupplements in refined food (Larrauri et al., 1999). DFconcentrates from vegetables and fruits may containimportant amounts of DF and have a better ratiobetween soluble (SDF) and insoluble dietary fiber(IDF) than cereal brans (Garau et al., 2007). SDF:IDFratio is important for health properties and also fortechnological characteristics; 30�50% of SDF and70�50% of IDF is considered a well-balanced propor-tion in order to obtain the physiological effectsassociated with both fractions (Grigelmo-Miguel andMartin-Belloso, 1999). Onions show an importantquantity of DF and a good SDF:IDF ratio that will havevarious metabolic and physiological effects (Jaimeet al., 2002). Ability of the fiber matrix to maintain itsphysical properties after being processed is quiteessential (Femenia et al., 1997).

Sterilization produces a decrease of IDF and anincrease of SDF, improving the SDF:IDF ratio. In gen-eral, uronic acids of IDF undergo solubilization afterthermal treatment, with transition to SDF. Swellingcapacity (SWC), which is related to fiber structure,suffers a decrease after sterilization as a result of IDFlosses, since insoluble fibers can adsorb water like asponge. However, water-holding capacity (WHC) doesnot undergo relevant changes with sterilization, sincethis treatment does not produce drastic changes in thefree hydroxyl groups that adsorb water throughhydrogen bonds. Cation exchange capacity (CEC)reduction could be related to the changes that pecticsubstances undergo after sterilization. Despite changesproduced by thermal treatment, sterilization would bea good method to stabilize onion by-products inorder to use them as a potential DF ingredient, sincephysico chemical properties of sterilized by-productsare generally higher than those of cellulose. Therefore,these by-products might have potential applications aslow-calorie bulk ingredients in DF enrichment, andwould be interesting in food products requiring oiland moisture retention (Benıtez et al., 2011).

Potato peel waste has been proposed as DF for bak-ing products (Arora and Camire, 1994). Cauliflowerhas a very high waste index and is an excellent sourceof protein (16.1%), cellulose (16%), and hemicellulose(8%). It is considered a rich source of DF and it pos-sesses both antioxidant and anticarcinogenic proper-ties. Stojceska et al. (2008) studied the incorporation ofcauliflower trimmings into ready-to-eat expanded pro-ducts (snacks) and their effect on the textural and func-tional properties of extrudates. It was found thataddition of cauliflower of up to 10% significantlyincreased the dietary fiber and levels of proteins. Thehigh crude fiber content of the vegetable pomace (intotal 20�65% DM) suggests its utilization as a crude

fiber bread improver. In bread and bakery goods, aswell as in pastry, cereals, and dairy products, theinvestigated carrot pomace works as a stabilizer,acidifying agent, preservative, or antioxidant.

6. SULFUR-CONTAINING BIOACTIVECOMPOUNDS

6.1 Cabbage Glucosinolates

Glucosinolates are a group of sulfur-containingplant secondary metabolites that are widely distrib-uted in brassica vegetables including broccoli, cauli-flower, lettuce, and cabbage (Cartea and Velasco,2008). Intact glucosinolates are generally located invacuoles and are inactive until plant cells are dam-aged, resulting in the release of glucosinolates fromthe vacuoles. Sulforaphane is a hydrolysis product ofglucosinolates, which is formed via the conversion ofglucoraphanin (one of the glucosinolates) by myrosi-nase under neutral or close to neutral conditions(pH 5�8). Sulforaphane is heat sensitive and its ther-mal susceptibility is much dependent on an experi-mental system (Shen et al., 2010). Outer leaves of whitecabbage (Brassica oleracea L. var. capitata), a typical by-product from a cabbage processing plant, have thepotential of being transformed into dietary fiber (DF)powder with high levels of antioxidants and anticarci-nogenic activities. However, losses of health-beneficialbioactive compounds in cabbage leaves may occurduring processing. As the processing of DF powderinvolves mechanical tissue damage (e.g., slicing,chopping) and thermal treatment (e.g., drying), it isinteresting to determine how the processing stepsaffect the sulforaphane content and degradation in theDF powder.

6.2 Methods of Processing

Tanongkankit et al. (2011) studied the effect of hotair drying at 40�70�C on the evolution of sulforaphanein cabbage. They found that the drying temperaturehad a significant effect on both the formation and deg-radation rates of sulforaphane. The results showedthat the formation of sulforaphane occurred when thecabbage temperature during drying was in the rangeof 25�53.5�C, and thermal degradation took placeonce the cabbage temperature exceeded this range. Asemi-empirical heat transfer and kinetic model was pro-posed to describe the change of sulforaphane through-out the drying process and it gives a very good fitto the experimental data. The results also showed thatalmost all sulforaphane formed during an early stageof drying degraded by the end of the drying process,

1116. SULFUR-CONTAINING BIOACTIVE COMPOUNDS


and only a small fraction of sulforaphane was retainedin the final DF powder. However, a previous studyreported that sulforaphane content of only approxi-mately 2.7 mg/L could inhibit the growth of HT29human colon cancer cells (Gamet-Payrastre et al.,2000). This indicates that the present DF powder couldstill provide anticarcinogenic properties. Alternatively,the hot air drying process may be stopped when thesulforaphane content is at a maximum level; sulforaph-ane can then be extracted at that maximum point.Drying at 60�C is suggested as an optimum conditionto obtain the highest retention of sulforaphane incabbage DF powder.

7. EXTRACTION PROCESSES FROMFOOD-AND-VEGETABLE WASTE

7.1 Extraction of Phenolic Compounds fromOlive Pomace

The high-pressure�high-temperature reactor hasbeen shown to be efficient for extraction of bioactivecompounds from olive pomace. Maximum total poly-phenols yield, expressed as units of caffeic acid equiv-alents per gram of dried pomace (45.2 mgCAE/gDP),was achieved at 180�C and 90 minutes, while totalflavonoids reached maximum value, expressed asunits of catechin equivalents per gram of dried pom-ace (15.3 mgCE/gDP), at 150�C and 60 min. A shortercontact time (30 min) was needed to extract the maxi-mum yield of o-diphenols (5.6 mgCAE/gDP) at 180�C.The preliminary results suggest that further completeoptimization of the proposed treatment, taking intoaccount the effects of extraction solvent and solid/liquid ratio, is necessary. Solid residue, derivedfrom the olive milling process, can be successfullyused as an inexpensive source of phenolic com-pounds so that food and pharmaceutical industriesmay benefit from this emerging technology(Aliakbarian et al., 2011).

7.2 Solvent and Enzyme-Aided AqueousExtraction of Goldenberry

Goldenberry (Physalis peruviana L.) pomace (seedsand skins) represents the waste obtained during juiceprocessing (around 27.4% of fruit weight). Ramadanet al. (2008) evaluated the potential of goldenberrypomace for use as a substrate for the production ofedible oil. The results provide important data that mayencourage development of goldenberry as acommercial crop and its industrial application. Threeextraction methods were examined for the best oil

yield. The n-hexane-extractable oil content of the rawby-products were estimated to be 19.3%. Enzymatictreatment with pectinases and cellulases followedby centrifugation in aqueous system, or followed bysolvent extraction, were also investigated for recoveryof oil from pomace fruit. Enzymatic hydrolysis ofpomace followed by extraction with n-hexane reducedthe extraction time and enhanced oil extractability upto a maximum of around 7.60%. The latter processesincreased the levels of protein, carbohydrates, fiber,and ash in the remaining meal. Regarding the oil com-position, there were no substantial changes noted inthe fatty acid pattern of the oils extracted with differ-ent techniques. Although goldenberry is a part of asupplemental diet in many parts of the world, infor-mation on the phytochemicals in this fruit is limited.Yet these phytochemicals may bring nutraceuticaland functional benefits to food systems. A variety ofhealth-promoting products improved from golden-berry pomace may include ground-dried skins andextracts obtained from skins and/or seeds. The levelsof polar lipids, unsaponifiables, peroxides, and pheno-lics in various extracts are associated with oxidativestability and radical scavenging activity.

7.3 Extraction of Antioxidants from PotatoPeels by Pressurized Liquids

Aqueous potato peel extracts were shown to be asource of phenolic acids, especially of chlorogenic, gal-lic, protocatechuic, and caffeic acids (Mader et al.,2009). The extracts display species-dependent antibac-terial but no mutagenic activity, and concentrations ofthe glycoalkaloids solanine and chaconine are belowtoxic threshold levels, if peel extracts are added at200 ppm to a foodstuff (Sotillo et al., 1998). Wijngaardet al. (2011) studied the extraction of antioxidants fromindustrial potato peel waste and optimized it withregards to ethanol concentration, temperature, andtime using solid�liquid extraction and pressurized liq-uid extraction of polyphenols. Both techniques wereoptimized by response surface methodology.Efficiency of extraction was optimized by measuringantioxidant activity, phenol content, and the level ofcaffeic acid. Conditions for optimal antioxidant activityas measured by the 2, 2-diphenyl-1-picrylhydrazylassay were 75% ethanol, 80�C, and 22 minutes withsolid�liquid extraction, resulting in an optimum activ-ity of 352 mg Trolox Equivalents/100 g DW potatopeel. Both ethanolic extractions resulted in higher anti-oxidant activities, polyphenol levels, and glycoalka-loids content than conventional extractions with 100%methanol and 5% acetic acid. Before the use as a foodingredient, glycoalkaloids should be removed; or the



extracts could be used for other purposes, for examplein the pharmaceutical industry. Glycoalkaloids havegained interest as possible precursors for the produc-tion of hormones (Schieber and Saldana, 2009), antibio-tics, and for use during certain skin diseases(Friedman, 2006).

7.4 Extraction of Phytochemicals fromCommon Vegetables

Chu et al. (2002) established a complete profile oftotal phenolic contents in vegetables by further digest-ing and extracting the bound phytochemicals. Theydeveloped the process of extraction of polyphenolsfrom 10 common vegetables as shown in Figure 6.3.Phenolic compounds in the edible part of thevegetables are present in both free and bound forms.Bound phenolics, mainly in the form of β-glycosides,may survive human stomach and small intestine diges-tion and reach the colon intact, where they are releasedand exert bioactivity. Bound phenolic contents arecomposed of bound-E and bound-W, which have dis-tinct extraction properties. Phenolic compoundsextracted by ethyl acetate are styled “bound-E”, andphenolic compounds recovered with water are styled“bound-W”. Bound phenolics of vegetables, mostly inester forms, are associated with cell wall components.Notably among them is ferulic acid (FA). FA has beenfound to be esterified to families, including pecticpolysaccharides, and cross-linked as a result of peroxi-dative activity. Owing to this protective mechanism, itis possible that bound phenolics can survive uppergastrointestinal digestion and may ultimately be bro-ken down in the colon by the microflora of the largeintestine. On average, approximately a fourth of thefresh vegetable phenolic compounds may be releasedand absorbed in the colon to furnish additional health

benefits locally, whereas potato and carrot couldrelease approximately half of their phytochemical con-tents in the colon. Epidemiological studies have shownan inverse correlation between vegetable consumptionand colon cancer occurrence (Voorrips et al., 2000).

Broccoli possessed the highest total phenolic con-tent, followed by spinach, yellow onion, red pepper,carrot, cabbage, potato, lettuce, celery, and cucumber.Red pepper had the highest total antioxidant activity,followed by broccoli, carrot, spinach, cabbage, yellowonion, celery, potato, lettuce, and cucumber. The phe-nolics antioxidant index (PAI) was proposed to evalu-ate the quality/quantity of phenolic contents in thesevegetables and was calculated from the corrected totalantioxidant activities by eliminating vitamin C contri-butions. Antiproliferative activities were also studiedin vitro using HepG2 human liver cancer cells(Table 6.4). Spinach showed the highest inhibitoryeffect, followed by cabbage, red pepper, onion, andbroccoli. On the basis of these results, the bioactivityindex (BI) for dietary cancer prevention was proposedto provide a simple reference for consumers to choosevegetables in accordance with their beneficial activi-ties. The BI is a half of the sum of total antioxidantactivity (AOA) score and antiproliferative activity(AA) score against liver cancer cells (Chu et al., 2002).The BI could be a new alternative biomarker for futureepidemiological studies in dietary cancer preventionand health promotion.

Focusing on separation processes, cost-effectiveapproaches proportional to the commercial value ofthe recovered molecule have been applied for recoveryof specific fine chemicals, such as solvent extraction,ion-exchange chromatography, and super-critical CO2

extraction. These processes often need specific

Vegetables

80% Acetone Extraction

Soluble

Soluble free Bound-E

EtAc-soluble Fraction Water-soluble Fraction

Solid Extraction

Bound-W

Concentration Concentration

EtAc Extraction

Insoluble

Base Digestion

Homogenization

FIGURE 6.3 Flowchart of extraction of phytochemicals from

vegetables. Source: Adapted from Chu et al. (2002).

TABLE 6.4 Bioactivity Index (BI), Antiproliferative Activity (AA)Score, and Antioxidant Activity (AOA) Score of Ten Vegetables

Vegetable BI AA AOA

Spinach 0.95 1.00 0.90

Red pepper 0.78 0.55 1.00

Broccoli 0.66 0.38 0.94

Cabbage 0.57 0.76 0.38

Carrot 0.45 0 0.91

Yellow onion 0.36 0.42 0.30

Celery 0.05 0 0.11

Potato 0.05 0 0.10

Lettuce 0.03 0 0.06

Cucumber 0.01 0 0.03

Source: Adapted from Chu et al. (2002).

1137. EXTRACTION PROCESSES FROM FOOD-AND-VEGETABLE WASTE


pretreatments to preserve the raw materials, such asstorage under modified atmosphere, microbial orchemical acidification, and pasteurization (Laufenberget al., 2003). Milling, crushing, steam explosion,and/or use of depolymerizing enzymes (e.g., macerase,β-glucosidase, and feruloyl esterase) are essential tofavor the extraction (Benoit et al., 2006).

8. WHEY AS A SOURCE OF BIOACTIVEPEPTIDES

8.1 Occurrence of Bioactive Peptides in Wheyand Other Dairy By-Products

Whey contains a large array of biologically activeproteins and peptides which, together with other compo-nents, have formed the basis for the use of whey inmedicinal applications for centuries. Apart from themajor whey proteins, β-lactoglobulin, α-lactalbumin, andglycomacropeptide, whey contains a number of otherproteins with potent bioactivity (Table 6.5) (Smithers,2008).

8.2 Functionality of Bioactive Peptides

A number of the above-mentioned bioactive wheypeptides, together with the parent protein source andproposed biological functionality, are shown inTable 6.6 (Smithers, 2008). Commercially, the mostpromising of these peptides is the effective antimicro-bial lactoferricin.

Milk-derived peptides have been shown in vivo toexert various activities affecting, for example, thedigestive, cardiovascular, immune, and nervous sys-tems. Dietary proteins are traditionally known to pro-vide a source of energy and the amino acids essentialfor growth and maintenance of various body functions.In addition, they contribute to the physico chemicaland sensory properties of protein-rich foods. In recentyears, food proteins have gained increasing value dueto the rapidly expanding knowledge about physiologi-cally active peptides. Milk proteins provide a richsource of peptides which are latent until released andactivated (e.g., during gastrointestinal digestion ormilk fermentation). Once activated, these peptides arepotential modulators of many regulatory processes inliving systems. Upon oral administration, bioactivepeptides may affect the major body systems, namely,the cardiovascular, digestive, immune, and nervoussystems (Figure 6.4), depending on their amino acidsequence. In the future, milk-derived bioactive pep-tides may be important health-sustaining componentsin food and in the prevention of diseases and condi-tions such as cardiovascular diseases, obesity, osteopo-rosis, and stress (Korhonen and Pihlanto, 2006).

8.2.1 Regulation of the Gastrointestinal System

Food-derived proteins and peptides may play impor-tant functions in the intestinal tract before hydrolysis toamino acids and subsequent absorption. These includeregulation of digestive enzymes and modulation ofnutrient absorption in the intestinal tract (Shimizu,2004).

8.2.2 Regulation of the Immune System

Milk protein hydrolysates and peptides derivedfrom caseins and major whey proteins can enhance

TABLE 6.6 Bioactive Whey-Derived Peptides

Protein Source Peptide Bioactivity (Some Putative)

α-Lactalbumin α-Lactophorin ACE inhibitor

β-Lactoglobulin β-Lactophorin Ileum stimulation

β-Lactotensin Ileum contraction

Serum albumin Albutensin ACE inhibitor, ileumcontraction

Serophorin Opioid activity

Glycomacropeptide 108�110;106�116

Antithrombotic

Lactoferrin Lactoferrin Antimicrobial

Source: Adapted from Smithers (2008).ACE, angiotensin-converting enzyme.

TABLE 6.5 Content of Minor Bioactive Proteins inCheese Whey

Protein Content (mg/L)

Lactoferrin 50�70

Lactoperoxidase 8�20

Immunoglobulins 300�600

Growth factors* , 0.06

IGF-I , 0.001

IGF-II , 0.001

PDGF , 0.0002

TGF-β , 0.01

FGF , 0.0001

Betacellulin , 0.002

Source: Adapted from Smithers (2008).*IGF, insulin-like growth factor; PDGF, platelet-derived growth factor; TGF,transforming growth factor; FGF, fibroblast growth factor.



immune cell functions, measured as lymphocyte prolif-eration, antibody synthesis, and cytokine regulation(Gill et al., 2000). Of special interest are peptidesreleased during milk fermentation with lactic acid bac-teria, as these peptides have been found to modulatethe proliferation of human lymphocytes, to down-regulate the production of certain cytokines, and tostimulate the phagocytic activities of macrophages(Matar et al., 2003; Meisel and FitzGerald, 2003). Ithas been also suggested that immunomodulatorymilk peptides may alleviate allergic reactions inatopic humans and enhance mucosal immunity in thegastrointestinal tract (Korhonen and Pihlanto, 2003).Furthermore, immunopeptides formed during milkfermentation have been shown to contribute to theantitumor effects observed in many studies withfermented milks (Matar et al., 2003). The fact thatcaseinophosphopeptides have been shown to exertcytomodulatory effects is of particular interest in thiscontext. Cytomodulatory peptides derived from caseinfractions inhibit cancer cell growth or stimulate theactivity of immunocompetent cells and neonatalintestinal cells (Meisel and FitzGerald, 2003).Glycomacropeptides (GMP) derived from κ-caseinmay have a beneficial role in modulating the gutmicroflora, as this macropeptide is known to promote

the growth of bifidobacteria due to its carbohydratecontent (Manso and Lopez-Fandino, 2004).

8.2.3 Regulation of the Cardiovascular System

Bioactive peptides from casein and whey may bedeployed in disease-specific applications such asblood pressure reduction and stress-related areas(e.g., in the case of mood-influencing peptides rich intryptophan). Peptides from casein may be used toenhance the solubility of minerals such as calciumand zinc, and hence increase the bioavailability ofthese minerals, or to inhibit angiotensin-convertingenzyme, which causes vasoconstriction and henceraises blood pressure.

8.2.4 Regulation of the Nervous System

Peptides with opioid activity have been identified invarious casein fractions hydrolyzed by digestiveenzymes (Teschemacher, 2003). These peptides areopioid receptor ligands with agonistic or antagonisticactivities. Opioid receptors are located in the nervous,endocrine, and immune systems as well as in thegastrointestinal tract of mammals. Thus, orally admin-istered opioid peptides may modulate absorption pro-cesses in the gut and influence the gastrointestinalfunction in two ways: first, by affecting smooth mus-cles, which reduces the transit time, and second, byaffecting the intestinal transport of electrolytes, whichexplains their antisecretory properties. The actualphysiological effects of milk-derived opioid peptidesremain, however, to be confirmed. β-Casein-derivedopioid peptides (β-casomorphins) or their precursorshave been detected in the human small intestine uponoral administration of casein or milk (FitzGerald andMeisel, 2003).

8.2.5 Antimicrobial Function

Immunoglobulins from vaccinated cows may beconsidered as natural antimicrobials with certainadvantages over synthetic antibiotics. Lactoferrin is anexample of a minor whey protein that has beenstudied in great detail; it is becoming increasingly clearthat it is important for nonspecific defense against bac-teria, fungi, and viruses. Oligosaccharides, glycolipids,and glycoproteins containing sialic acid residues mayhave a role as anti-infectives.

8.2.6 Growth Factor Activity

Pioneering work over the past approximately fifteenyears has laid the foundation for exploitation of theremarkable cell growth promotional activity of anextract from cheese whey containing a plurality ofgrowth factors (Table 6.5).

Antihypertensive

Cardiovascularsystem

Nervous system

Gastrointestinalsystem

Immune system

Antioxidative

Antithrombotic

Hypocholesterolemic

Mineral-binding

Anti-appetizing

Antimicrobial

Immunomodulatory

Cytomodulatory

Opioid• agonist activity• antagonist activity

FIGURE 6.4 Physiological functionality of milk-derived bioac-

tive peptides. Source: Korhonen and Pihlanto (2006).

1158. WHEY AS A SOURCE OF BIOACTIVE PEPTIDES


8.3 Commercial Dairy Products ContainingBioactive Peptides

An increasing number of ingredients containingspecific bioactive peptides based on casein or wheyprotein hydrolysates have been launched on themarket within the past few years or are currentlyunder development by international food companies.Korhonen and Pihlanto (2006) reported several exam-ples of these commercial products, their health func-tion, and manufacturers.

8.4 Commercial-Scale Production

Industrial-scale technologies suitable for the com-mercial recovery of bioactive milk peptides have beendeveloped and launched recently. These technologiesare based on novel membrane separation and ionexchange chromatographic methods being employedby the emerging dairy ingredient industry. Emergingtechnologies for generation and concentration of bio-active peptides include high-pressure processing,high-power ultrasound, pulsed electric field, andmicrofluidization (Smithers, 2008).

Controlled fermentation of raw materials rich inproteins by known lactic acid bacteria strains may bedeveloped on the commercial scale with respect tocontinuously operating bioreactors. Alternatively,commercial production of specific peptide sequencescould be enabled through recombined enzyme tech-nology utilizing certain production strains, orthrough the use of purified proteolytic enzymes iso-lated from suitable microorganisms (Korhonen andPihlanto, 2003). Before commencing the developmentof nutraceuticals from whey and milk by-products, anumber of technological and marketing issues shouldbe addressed. On the technological side, the questionof the cost of the process required to manufacturethe desired protein, peptide, or special lipid shouldbe dealt with at a very early stage, together withhow to valorize the non-bioactive residual raw mate-rial. The selected technology should preferably beproprietary, and the application of the bioactiveshould be protected by patents. Food safety is alsoan important feature. On the marketing side, cost-effectiveness of the ingredient and ease of incorpo-ration into a good-tasting end product are vital.Claiming a message that can be understood by con-sumers or is allowed by legal authorities is a furtherprerequisite for successful market introduction. Quickentry into the market is sometimes possible when alarge body of circumstantial evidence from the scien-tific literature is available. Animal models are some-times used for proof of concept. To be able to makefirm health claims, human clinical data are needed,

preferably with the end product containing the bioac-tive ingredient (Steijns, 2001).

9. PRODUCT DEVELOPMENT,MARKETING, AND CONSUMER

ACCEPTANCE OF FUNCTIONAL FOODS

Consumer acceptance of the concept of functionalfoods has been widely recognized as a key success fac-tor for market orientation, consumer-led productdevelopment, and successfully negotiating marketopportunities. Acceptance, however, is determined bya host of factors such as primary health concerns, con-sumers’ familiarity with functional food concepts andwith the functional ingredients, the nature of the car-rier product, the manner of health effect communica-tion, etc. Consumers’ knowledge and awareness of thehealth effects of newly developed functional ingredi-ents seems to be rather limited; therefore, there is astrong need for specific communication activities toconsumers in this respect. Different surveys haveshown that consumer acceptance of functional foods isfar from being unconditional, with one of the mainconditions for acceptance pertaining to taste, besidesproduct quality, price, convenience, and trustworthi-ness of health claims. As a rule, consumers seem toevaluate functional foods first and foremost as foods.Functional benefits may provide added value to consu-mers but cannot outweigh the sensory properties offoods (Siro et al., 2008).

On the other hand, Europeans in general are far morecritical of new products and technologies (e.g., GMOfood, irradiated food) than are American consumers(Lusk and Rozan, 2005). They are not only suspicious ofthe safety of novel foods, but they are critical of thewhole process through which food production becomesmore and more anonymous and distanced from every-day life (Poppe and Kjnes, 2003). Therefore, it can behypothesized that Europeans’ acceptance of functionalfoods is less unconditional, better thought out, and withmore concerns and reservations than in the USA. Thismay also be influenced by the recent sequence of foodsafety scares (e.g., BSE, dioxins, foot-and-mouth disease,E. coli, aviatic pneumonia, acrylamid) (Verbeke, 2005).

10. CONCLUSIONS

Fruits and vegetables represent an untapped reser-voir of various nutritive and non nutritive phytochem-icals with potential cancer chemopreventive activity.The phytochemicals such as phenolic compounds,namely flavonoids, are the major contributors to theantioxidant capacity of the apple, grape, and olive



pomace, onion/potato peels, and other common FVW.Recent research suggests that in humans, these plantpolyphenols provide important health benefits relatedto metabolic syndrome, cancer, brain health, and theimmune system. The relatively low toxicity and poten-tial efficacy of most of these agents make them attrac-tive to a large sector of the population.

Various grape-based products of different origin arecurrently available in the US market: 22 grape seedproducts, 5 grape extracts, and 7 red wine powders(Shrikhande, 2000). Because of their beneficial properties,winery by-products are now being sold to the rapidlygrowing dietary supplement industry (Arvanitoyanniset al., 2006). However, more studies are needed in high-risk populations for cancer of specific organs or siteswith standardized grape seed extract (GSE) preparationsto establish the dose regimen and to determine pharma-cologically achievable levels of biologically active consti-tuents in the plasma/target organ. These studies wouldalso help establish any toxicity associated with long-termadministration of GSE (Kaur et al., 2009). Anthocyanins,carotenoids, betalains, and lycopenes represent the majorgroups of colored phenolic compounds in FV residues,which also exert a strong antioxidant activity. TheEuropean Commission (EC) allows the use of anthocya-nins as food dyes in drinks, marmalades, candies, icecreams, and pharmaceutical products. FV by-productssuch as apple, pear, orange, peach, black currant, cherry,artichoke, asparagus, onion, cauliflower, potato peels,and carrot pomace are also used as sources of dietaryfiber supplements in refined food. From a scientific pointof view, further studies are needed to demonstrate theefficacy and safety of nutraceuticals recovered from FVby-products. Efficient purification steps are necessarybefore bioactive compounds can be used as natural foodingredients. These processing steps must remove anynatural and anthropogenic toxins that might be presentin the raw material (Schieber, 2009).

Today’s achievements in separation techniques inthe dairy industry and enzyme technology offer oppor-tunities to isolate, concentrate, or modify bioactivepeptides from whey and other milk by-products, sothat their application in functional foods, dietary sup-plements, nutraceuticals, and healing foods has becomepossible. So far, antihypertensive, mineral-binding, andanticarcinogenic peptides have been most studied fortheir physiological effects. A few commercial develop-ments have been launched on the market, andthis trend is likely to continue alongside increasingknowledge about the functionalities of the peptides.However, molecular studies are needed to assess themechanisms by which the bioactive peptides exert theiractivities. This research area is currently considered tobe the most challenging one, due to the understandingthat most known bioactive peptides are not absorbed

from the gastrointestinal tract into the blood circulation.Their effect is likely to be mediated directly in the gutlumen or through receptors on the intestinal cell wall.In this respect, the target function of the peptide con-cerned is of utmost importance. It is expected that inthe near future such targets shall be the following life-style-related disease groups: (a) cardiovascular dis-eases, (b) cancers, (c) osteoporosis, (d) stress, and(e) obesity. Peptides derived from dietary proteins offera promising approach to prevent, control, and eventreat such disease conditions through a regulated diet(Korhonen and Pihlanto, 2006). Whey components, par-ticularly the proteins and peptides, will increasingly bepreferred as ingredients for functional foods and nutra-ceuticals, and as active medicinal agents, built upon thestrong consumer trend for health and wellbeing andcontinuing discovery and substantiation of the biologi-cal functionality of whey constituents (Smithers, 2008).

Increased health awareness and consumer confi-dence coupled with an aging population have drivendemand for products that improve the quality of life,have specific health benefits, and can be used by con-sumers to self-medicate. The global consumption offunctional foods and drinks increased by a compoundannual rate of over 6% between 2003 and 2008, andgrowth is predicted to continue over the next years(www.just-food.com). However, many processesdescribed so far have been performed on a laboratoryscale, or at best on a pilot plant scale. In order for theseapproaches to find their way into industrial reality,they must be economically feasible, which sometimesmay pose a challenge because of the additional proces-sing steps needed for valorization.

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